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New research into the genetic diversity of the most feared malaria parasite, Plasmodium falciparum, indicates that making an effective malaria vaccine may be even more difficult than scientists had thought.
Three studies published online in Nature Genetics this week (10 December) probe the parasite’s genetic structure to find out which genes vary most, in order to identify potential targets for malaria vaccines.
It was already known that some genes, and the proteins that they code for, are variable, but this new work shows that there are many more variations than were previously recognised.
“The parasite genome is very plastic,” said Emmanouil Dermitzakis of the Wellcome Trust Sanger Institute, lead researcher of one of the studies.
“It carries the scars of its battle against its three main challenges — our rapidly evolving human immune system, the defensive responses of the mosquito and the insecticides and drugs we use to challenge it.”
P. falciparum kills between 1-2 million people each year, mostly young children in Africa.
“For the first time, we have comprehensive maps that detail areas of variation — the regions where the effects of our defences are marked in the parasite genome,” said Matthew Berriman of the Wellcome Trust Sanger Institute, who co-led the study with Dermitzakis.
“When we attack, the parasite responds and that is marked by the changes in the parasite DNA that we observe,” he said.
The team provided the first sequence of the related parasite Plasmodium reichenowi, which infects chimpanzees, compared it to P. falciparum and examined the evolutionary differences between the two.
They found that the malaria parasite has many tools to use in its battle to infect humans, the most significant being the possibility to ‘cloak’ itself in any one of a suite of cellular disguises.
If one variant is successfully treated, another might rise from the background making development of vaccines to combat malaria very difficult.
“We found that genes that are active in red blood cells and genes that are predicted to interact with host cells were especially variable,” said co-researcher Daniel Jeffares, also at the Wellcome Trust Sanger Institute.
The study identified genes most likely to be good targets for long-lasting new treatments, which would be parts of the genome that evolve less quickly.
“Looking at the evolution of categories of genes can point to those that are essential to the parasite’s lifestyle and are also likely to be stable – and hence most valuable for new treatments,” said Jeffares.
Brian Greenwood, clinician and malaria expert at the London School of Hygiene and Tropical Medicine, said the studies indicate that making a highly effective malaria vaccine may be even more difficult than thought so far.
“The immune response induced by a vaccine made from one strain of parasite may not give good protection against another strain – as is seen in the case of flu vaccines,” he warned.“On the positive side, it provides us with some more important information on the structure of the malaria parasite, which is bound to help in the control of this infection in the long term,” Greenwood told SciDev.Net.
Links to full papers in Nature Genetics:Genome-wide variation and identification of vaccine targets in the Plasmodium falciparum genome
A genome-wide map of diversity in Plasmodium falciparum
Genome variation and evolution of the malaria parasite Plasmodium falciparum
References:Nature Genetics doi: 10.1038/ng1924 (2006)
Nature Genetics doi: 10.1038/ng1930 (2006)
Nature Genetics doi: 10.1038/ng1931 (2006)